Insulin-stimulated chemokinesis in normal human neutrophils is dependent on D-glucose concentration and sensitive to inhibitors of tyrosine kinase and phosphatidylinositol 3-kinase.
This study shows that D-glucose and insulin, alone and in certain combinations, have chemokinetic effects on neutrophil granulocytes from healthy humans. A stimulatory chemokinetic effect of insulin was present at 40-160 microU/mL insulin but only in the presence of 5 mM, and not at 15 mM, D-glucose. D-Glucose alone dose-dependently increased the neutrophil locomotion, showing a maximum effect at 5-15 mM and a return toward the basal locomotion at 25 mM glucose. Because the stimulatory chemokinetic effects of 5 and 15 mM D-glucose alone were the same, it seems that the high glucose level does not inhibit the basic motile properties of the cells but may generate intracellular signals interfering with the signal transduction underlying the insulin effect. The tyrosine kinase inhibitor, genistein, or the phosphatidylinositol 3-kinase inhibitor, wortmannin, abolished the chemokinetic effect of 160 microU/mL insulin in the presence of 5 mM D-glucose. This indicates that the insulin effect on locomotion is indeed mediated by receptor-associated tyrosine kinase activation and involving phosphatidylinositol 3-kinase.
Oldenborg
P A
PA
Department of Histology and Cell Biology, Umeå University, Sweden. per-arne.oldenborg@histocel.umu.se
Sehlin
J
J
D000730:Androstadienes / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007328:Insulin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D005947:Glucose; D000077191:Wortmannin